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See detailINTERROGATING INTRA-TUMORAL HETEROGENEITY AND TREATMENT RESISTANCE IN GLIOBLASTOMA PATIENT-DERIVED XENOGRAFT MODELS USING SINGLE-CELL RNA SEQUENCING
Yabo, Yahaya Abubakar UL

Doctoral thesis (2022)

Despite available treatment options for glioblastoma (GBM), GBM has one of the poorest prognosis, resist treatment, and recur aggressively in the majority of cases. Intra-tumoral heterogeneity and ... [more ▼]

Despite available treatment options for glioblastoma (GBM), GBM has one of the poorest prognosis, resist treatment, and recur aggressively in the majority of cases. Intra-tumoral heterogeneity and phenotypic plasticity are major factors contributing to treatment resistance and underlie tumor escape in GBM. Several potential therapeutic agents showing promising therapeutic effects against GBMs at the preclinical level failed to translate into effective therapies for GBM patients. This is partly attributed to the inadequacy of preclinical models to fully recapitulate the complex biology of human GBMs. This project aimed to characterize the transcriptomic heterogeneity and understand the dynamic GBM ecosystem in patient-derived xenograft (PDOX) models at the single-cell level. To achieve this aim, I established cell purification and cryopreservation protocols that enable the generation of high-quality single-cell RNA seq data from PDOX models including longitudinal and treated PDOXs. Different computational strategies were used to interrogate the transcriptomic features as well as the interactions between GBM cells and the surrounding microenvironment. This work critically analyzed and discussed key components contributing to intra-tumoral heterogeneity and phenotypic plasticity within the GBM ecosystem and their potential contributions to treatment resistance. Here, we provide evidence that PDOX models retain histopathologic and transcriptomic features of parental human GBMs. PDOX models were further shown to recapitulate major tumor microenvironment (TME) components identified in human GBMs. Cells within the GBM ecosystem were shown to display GBM-specific transcriptomic features, indicating active TME crosstalk in PDOX models. Tumor-associated microglia/macrophages were shown to be heterogeneous and display the most prominent transcriptomic adaptations following crosstalk with GBM cells. The myeloid cells in PDOXs and human GBM displayed a microglia-derived TAMs signature. Notably, GBM-educated microglia display immunologic features of migration, phagocytosis, and antigen presentation that indicates the functional role of microglia in the GBM TME. Taking advantage of a cohort of longitudinal PDOXs and treated PDOX models, I demonstrated the utility of PDOX models in elucidating longitudinal changes in GBM. We show that temozolomide treatment leads to transcriptomic adaptation of not only the GBM tumor cells but also adjacent TME components. Overall, this work further highlights the importance and the clinical relevance of PDOX models for the testing of novel therapeutics including immunotherapies targeting certain tumor TME components in GBM. [less ▲]

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See detailInterrogating surface length spectra and quantifying isospectrality
Parlier, Hugo UL

in MATHEMATISCHE ANNALEN (2018), 370(3-4), 1759-1787

This article is about inverse spectral problems for hyperbolic surfaces and in particular how length spectra relate to the geometry of the underlying surface. A quantitative answer is given to the ... [more ▼]

This article is about inverse spectral problems for hyperbolic surfaces and in particular how length spectra relate to the geometry of the underlying surface. A quantitative answer is given to the following: how many questions do you need to ask a length spectrum to determine it completely? In answering this, a quantitative upper bound is given on the number of isospectral but non-isometric surfaces of a given genus. [less ▲]

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See detailInterrogating surface length spectra and quantifying isospectrality
Parlier, Hugo UL

E-print/Working paper (2016)

This article is about inverse spectral problems for hyperbolic surfaces and in particular how length spectra relate to the geometry of the underlying surface. A quantitative answer is given to the ... [more ▼]

This article is about inverse spectral problems for hyperbolic surfaces and in particular how length spectra relate to the geometry of the underlying surface. A quantitative answer is given to the following: how many questions do you need to ask a length spectrum to determine it completely? In answering this, a quantitative upper bound is given on the number of isospectral but non-isometric surfaces of a given genus. [less ▲]

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See detailInterrogating the effect of enzyme kinetics on metabolism using differentiable constraint-based models
Wilken, St Elmo; Besançon, Mathieu; Kratochvil, Miroslav UL et al

in Metabolic Engineering (2022)

Metabolic models are typically characterized by a large number of parameters. Traditionally, metabolic control analysis is applied to differential equation-based models to investigate the sensitivity of ... [more ▼]

Metabolic models are typically characterized by a large number of parameters. Traditionally, metabolic control analysis is applied to differential equation-based models to investigate the sensitivity of predictions to parameters. A corresponding theory for constraint-based models is lacking, due to their formulation as optimization problems. Here, we show that optimal solutions of optimization problems can be efficiently differentiated using constrained optimization duality and implicit differentiation. We use this to calculate the sensitivities of predicted reaction fluxes and enzyme concentrations to turnover numbers in an enzyme-constrained metabolic model of Escherichia coli. The sensitivities quantitatively identify rate limiting enzymes and are mathematically precise, unlike current finite difference based approaches used for sensitivity analysis. Further, efficient differentiation of constraint-based models unlocks the ability to use gradient information for parameter estimation. We demonstrate this by improving, genome-wide, the state-of-the-art turnover number estimates for E. coli. Finally, we show that this technique can be generalized to arbitrarily complex models. By differentiating the optimal solution of a model incorporating both thermodynamic and kinetic rate equations, the effect of metabolite concentrations on biomass growth can be elucidated. We benchmark these metabolite sensitivities against a large experimental gene knockdown study, and find good alignment between the predicted sensitivities and in vivo metabolome changes. In sum, we demonstrate several applications of differentiating optimal solutions of constraint-based metabolic models, and show how it connects to classic metabolic control analysis. [less ▲]

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See detailInterrogations autour d'un droit fondamental: l'appel
Ravarani, Georges UL

in Justices et droit du procès, Mélanges en l'honneur de Serge Guinchard (2010)

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See detailInterrupting hope.
Biesta, Gert UL

in Philosophy of Education Yearbook (2007)

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See detailInterrupting the politics of learning
Biesta, Gert UL

in Power and Education (2013), 5(1), 4-15

In this article, the author raises critical questions about the notion of 'learning', the language of 'learning' and the discourse of 'learning'. The analytical and critical device used is the idea of the ... [more ▼]

In this article, the author raises critical questions about the notion of 'learning', the language of 'learning' and the discourse of 'learning'. The analytical and critical device used is the idea of the 'politics of learning', through which the author highlights the powerful work that is being done by, and which at the very same time is hidden behind, the discourse of 'learning'. The author focuses on the field of lifelong learning, not only because it is here that claims about and demands for learning are most explicitly articulated, but also because this field, through both policy and research, is contributing most strongly to an apparent 'common sense' about learning in contemporary societies. Based on this analysis, the author argues that there is a need for an interruption of the politics of learning in order to reclaim the emancipatory potential of education. [less ▲]

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See detailThe interruptive effect of pain in a multitask environment: an experimental investigation.
Van Ryckeghem, Dimitri UL; Crombez, Geert; Eccleston, Christopher et al

in The journal of pain : official journal of the American Pain Society (2012), 13(2), 131-8

UNLABELLED: Daily life is characterized by the need to stop, start, repeat, and switch between multiple tasks. Here, we experimentally investigate the effects of pain, and its anticipation, in a multitask ... [more ▼]

UNLABELLED: Daily life is characterized by the need to stop, start, repeat, and switch between multiple tasks. Here, we experimentally investigate the effects of pain, and its anticipation, in a multitask environment. Using a task-switching paradigm, participants repeated and switched between 3 tasks, of which 1 predicted the possible occurrence of pain. Half of the participants received low intensity pain (N = 30), and half high intensity pain (N = 30). Results showed that pain interferes with the performance of a simultaneous task, independent of the pain intensity. Furthermore, pain interferes with the performance on a subsequent task. These effects are stronger with high intensity pain than with low intensity pain. Finally, and of particular importance in this study, interference of pain on a subsequent task was larger when participants switched to another task than when participants repeated the same task. PERSPECTIVE: This article is concerned with the interruptive effect of pain on people's task performance by using an adapted task-switching paradigm. This adapted paradigm may offer unique possibilities to investigate how pain interferes with task performance while people repeat and switch between multiple tasks in a multitask environment. [less ▲]

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See detailAn intersectional approach on primary school textbooks
Kerger, Sylvie UL; Brasseur, Laurence

in An intersectional approach on primary school textbooks (2022)

Textbooks play an important part in children's schooling. They have an obvious educational purpose and exist to convey knowledge, but their worth goes beyond the simple school framework. Teaching ... [more ▼]

Textbooks play an important part in children's schooling. They have an obvious educational purpose and exist to convey knowledge, but their worth goes beyond the simple school framework. Teaching materials, and particularly textbooks, have an essential role in the socialisation of children through the values they communicate. Based on these observations, we conducted an extensive study of gender representations in textbooks used in Luxembourg primary schools (Kerger & Brasseur, 2021). Through a quantitative and qualitative analysis of the number of characters and the type of activities in which they are represented, we were able to uncover the norms and stereotypes found in these textbooks. [less ▲]

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See detailIntersectional Inequalities in Science
Kozlowski, Diego UL

Presentation (2022, November 16)

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See detailIntersectional inequalities in science
Kozlowski, Diego UL

Scientific Conference (2022, April 28)

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See detailIntersectional Inequalities in Science
Kozlowski, Diego UL; Larivière, Vincent; Sugimoto, Cassidy R. et al

in Proceedings of the National Academy of Sciences of the United States of America (2022), 119(2), 2113067119

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few ... [more ▼]

The US scientific workforce is primarily composed of White men. Studies have demonstrated the systemic barriers preventing women and other minoritized populations from gaining entry to science; few, however, have taken an intersectional perspective and examined the consequences of these inequalities on scientific knowledge. We provide a large-scale bibliometric analysis of the relationship between intersectional identities, topics, and scientific impact. We find homophily between identities and topic, suggesting a relationship between diversity in the scientific workforce and expansion of the knowledge base. However, topic selection comes at a cost to minoritized individuals for whom we observe both between- and within-topic citation disadvantages. To enhance the robustness of science, research organizations should provide adequate resources to historically underfunded research areas while simultaneously providing access for minoritized individuals into high-prestige networks and topics. [less ▲]

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See detailIntersectional Inequalities in Science
Kozlowski, Diego UL

Presentation (2021, December 06)

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See detailIntersectionality and Adolescent Mental Well-being: A Cross-Nationally Comparative Analysis of the Interplay Between Immigration Background, Socioeconomic Status and Gender
Kern, Matthias Robert UL; Duinhof, Elisa L.; Walsh, Sophie D. et al

in Journal of Adolescent Health (2020), 66(6), 12-20

Purpose: Intersectionality theory highlights the importance of the interplay of multiple social group memberships in shaping individual mental well-being. This article investigates elements of adolescent ... [more ▼]

Purpose: Intersectionality theory highlights the importance of the interplay of multiple social group memberships in shaping individual mental well-being. This article investigates elements of adolescent mental well-being (life dissatisfaction and psychosomatic complaints) from an intersectional perspective. It tests mental well-being consequences of membership in combinations of multiple social groups and examines to what extent such intersectional effects depend on the national context (immigration and integration policies, national-level income, and gender equality). Methods: Using Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy, we assessed the role of the national context in shaping the interplay between immigration background, socioeconomic status, and gender, using data from 33 countries from the 2017/2018 Health Behaviour in School-aged Children survey. Results: We found no uniform intersectionality effects across all countries. However, when allowing the interplay to vary by national context, results did point toward some intersectional effects. Some aggravated negative effects were found for members of multiple disadvantaged social groups in countries with low levels of income equality and restrictive migration policies, whereas enhanced positive effects were found for members of multiple advantaged groups in these countries. Similarly, mitigated negative effects of membership in multiple disadvantaged groups were shown in countries with higher levels of income equality and more inclusive migration policies, whereas mitigated positive effects were found for multiply advantaged individuals. Although for national-level gender equality results pointed in a similar direction, girls’ scores were counterintuitive. High national-level gender equality disproportionately benefitted groups of disadvantaged boys, whereas advantaged girls were doing worse than expected, and reversed effects were found for countries with low gender equality. Conclusions: To fully understand social inequalities in adolescent mental well-being, the interplay between individual-level and national-level indicators must be explored. [less ▲]

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See detailIntersections of Finitely Generated Maximal Partial Clones
Couceiro, Miguel UL; Haddad, Lucien

in Journal of Multiple-Valued Logic and Soft Computing (2012), 19(1-3), 85-94

Let A be a finite non-singleton set. For A ={0, 1} we show that the set of all self-dual monotonic partial functions is a not finitely generated partial clone on {0, 1} and that it contains a family of ... [more ▼]

Let A be a finite non-singleton set. For A ={0, 1} we show that the set of all self-dual monotonic partial functions is a not finitely generated partial clone on {0, 1} and that it contains a family of partial subclones of continuum cardinality. Moreover, for |A| ≥ 3, we show that there are pairs of finitely generated maximal partial clones whose intersection is a not finitely generated partial clone on A. [less ▲]

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See detailIntersections with Slupecki Partial Clones on a Finite Set
Schölzel, Karsten UL; Haddad, Lucien

in Multiple-Valued Logic (ISMVL), 2013 IEEE 43rd International Symposium on (2013, May)

We study intersections of partial clones on the k-element set with k ≥ 2. More precisely we consider intersections of Slupecki partial clones with non-Slupecki maximal partial clones on k.

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See detailIntersektionalität in der Sonderpädagogik. Perspektiven für die Analyse der Wechselbeziehungen von Behinderung und anderen Ungleichheitsdimensionen
Hinni, Chantal; Zurbriggen, Carmen UL

in Vierteljahresschrift für Heilpädagogik und ihre Nachbarsgebiete (2018), 87(2), 167-172

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See detailIntersektionalität und Gouvernementalität. Die Problematisierung der Prostitution in Luxemburg um 1900 bis zum Ende der Zwischenkriegszeit
Mauer, Heike UL

Doctoral thesis (2015)

My dissertation “Intersektionalität und Gouvernementalität. Die Problematisierung der Prostitution in Luxemburg um 1900 bis zum Ende der Zwischenkriegszeit” pursues three scientific aims: first it ... [more ▼]

My dissertation “Intersektionalität und Gouvernementalität. Die Problematisierung der Prostitution in Luxemburg um 1900 bis zum Ende der Zwischenkriegszeit” pursues three scientific aims: first it advances political and feminist theory, secondly it contributes to Luxembourgian social, political and gender history by developing thirdly a fresh methodology. The object of investigation is the historical problematization of prostitution in Luxembourg – that is the perception and 'government' of prostitution as a problem of societal and individual moral conduct. My thesis is the first major historical publication, dedicated to the analysis of prostitution in Luxembourg. The main research question pursued was to identify the intersectional dimensions of this problematization of prostitution and to identify its inherent logics of power. The innovative, theory-driven method used for investigation rested on the connection of two theoretical concepts: intersectionality (a tool to understand gender as always related to other dimensions of power and inequality such as class, race, nation, citizenship, etc.) and governmentality (a distinct mode of power, which is - unlike sovereignty or discipline – characterized by the capacity to govern the conduct of others as well as by “technologies of the self” [Foucault]). By developing this methodology, my thesis also advances political and feminist theory. I highlight actual shortfalls of intersectional approaches and strengthen the tools analytical capacities to investigate power relations. I developed an understanding of intersectionality focusing on the processes and modes of how power is exercised, transcending static approaches, which perceive intersectionality solely in terms of inequalities. Empiricaly I demonstrated, that power was exercised intersectionally through the problematization of prostitution, while the problematization adressed different intersectional subjects differently: the prostitute was identified by a logic of suspicion as a poor foreign woman, who was deported in order to 'morally cleanse' the nation. Through the government of moral conduct, Luxembourgian working class women were encouraged to be good housewives in order to prevent their husbands from falling for prostitution in bars. [less ▲]

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See detailL'intersubjectivité de l'entretien annuel d'évaluation, levier de la reconnaissance psychologique au travail?
Tancredi, Ernestina UL

Doctoral thesis (2020)

This paper aims to observe the impact of the Annual Appraisal Interview (AAI) on psychological recognition in the workplace through its intersubjectivity. Although performance reviews are implicitly ... [more ▼]

This paper aims to observe the impact of the Annual Appraisal Interview (AAI) on psychological recognition in the workplace through its intersubjectivity. Although performance reviews are implicitly discussed in the literature on recognition at work, the link between these two concepts is very poorly developed. The first part of the study details the theoretical foundations of recognition at work from a polysemic and transdisciplinary perspective. Two models of models of psychological recognition at work (Bourcier & Palobart, 1997; Deci & Ryan, 1985) are retained. By also addressing the dual character (objective / subjective) of the AAI, its importance for human relations and its purpose of recognition at work, this part highlights its main intersubjective elements: the participation of the appraisees, their individuality, the skills of the appraiser, the actual work of the appraisee and the fairness of the feedback. The second part presents the research methodology based on semi-structured interviews and questionnaires with three target groups (HR managers, appraisers, appraisees) of around one hundred organizations located in the Grand Duchy of Luxembourg. Analysis of the results shows that the AAI confers six types of psychological recognition (existential recognition, recognition of investment, recognition of results, need for autonomy, need for competence and need for social belonging) through the intersubjective levers of the AAI, but to varying degrees. A classification on a "person-work" basis of the AAI levers and the six types of recognition will allow managers to activate the appropriate levers in order to achieve a balance between the types of psychological recognition. [less ▲]

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See detailIntersymbol and Intercarrier Interference in OFDM Systems: Unified Formulation and Analysis
Cruz–Roldán, Fernando; Alves Martins, Wallace UL; García, Fausto G. et al

E-print/Working paper (2020)

A unified matrix formulation is presented for the analysis of intersymbol and intercarrier interference in orthogonal frequency-division multiplexing (OFDM) systems. The proposed formulation relies on six ... [more ▼]

A unified matrix formulation is presented for the analysis of intersymbol and intercarrier interference in orthogonal frequency-division multiplexing (OFDM) systems. The proposed formulation relies on six parameters and allows studying various schemes, including those with windowing in the transmitter and/or in the receiver (called windowed OFDM systems), which may add cyclic suffix and/or cyclic prefix (CP), besides the conventional CP-OFDM. The proposed framework encompasses seven different OFDM systems. It considers the overlap-and-add procedure performed in the transmitter of windowed OFDM systems, being jointly formulated with the channel convolution. The intersymbol and intercarrier interference, caused when the order of the channel impulse response is higher than the number of CP samples, is characterized. A new equivalent channel matrix that is useful for calculating both the received signal and the interference power is defined and characterized. Unlike previous works, this new channel matrix has no restrictions on the length of the channel impulse response, which means that the study is not constrained to the particular case of two or three data blocks interfering in the received signal. Theoretical expressions for the powers of three different kinds of interference are derived. These expressions allow calculating the signal-to-interference-plus-noise ratio, useful for computing the data rate of each OFDM system. The proposed formulation is applied to realistic examples, showing its effectiveness through comparisons based on numerical performance assessments of the considered OFDM systems. [less ▲]

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